Virus receptor-binding domain (RBD) are found in particular in the envelope glycoprotein (Env) of viruses and are able to bind to membrane receptors of different target cells.
Gamma and deltaretroviruses have been shown to interact with cell surface through active receptors that belong to the multimembrane protein family. Those receptors for which a function has been identified (or most certainly those with no identified function) are directly involved in cellular metabolism.
Retroviral envelope-derived probes, which can be used for specific, high-affinity tagging of metabolic transporters on human cells, have been disclosed in WO 2010/079208. These transporters carry a wide variety of metabolites, including, but not limited to: neutral amino acids (AA), cationic AA, glucose, heme and vitamins.
Retroviral envelope-derived probes of WO 2010/079208 have been used for the detection of membrane receptors present in a target cell such as haematopoietic stem cells, such as CD34 cells, or differentiated cells such as B-cells or T-cells.
Myelocyte and monocyte lines (granulocytes) play a major role in body's response to stress. During infestation by pathogens, regulated signals by epithelial and inflammatory cells get position to coordinate innate and acquired immunity. A rapid intervention is necessary and involves a complete reprogramming of quiescent circulating myelocyte and monocyte lines to be activated and migrate to injury sites. This turn over, requiring gene transcription and protein production, is energy-dependent. It needs nutrients and metabolites absorption that can be reflected with an increase of metabolic transporters at the surface of inflammatory cells.
Asthma is a chronic disease characterized by bronchoconstriction, wheezing, cough and breath difficulties during exacerbations. This pathology affects about 300 million worldwide. The airway inflammation is generated by an influx of myelocyte and monocyte lines in the lungs; mostly eosinophils seem to be implied as well as neutrophils.
Allergy is also a disorder of the immune system caused by the suractivation of mast cells and basophils when they identify allergen-specific immunoglobulin IgE. Activated cells release histamine and cytokines maintaining and aggravating the reaction of inflammation. Allergic crisis could manifest minor symptoms but also serious reactions as respiratory difficulties and coma.
Cystic fibrosis (also known as CF) is a common disease which affects the entire body, causing progressive disability and often early death.
Difficulty breathing is the most serious symptom and results from frequent lung infections that are treated, though not cured, by antibiotics and other medications. A multitude of other symptoms, including sinus infections, poor growth, diarrhea, and infertility result from the effects of CF on other parts of the body.
The increasing importance of these pathologies makes the discovery of a rapid detection of them or of therapeutical agents highly desirable.
One of the aims of the present invention is to provide RBD for the detection of membrane receptors present in granulocytes indicating an inflammatory state.
Another aim of the invention is to provide a diagnosis and/or prognosis process of an inflammation state.
Still another aim of the invention is to provide a method for measuring the therapeutic efficacy of a potential anti-inflammatory drug in a mammal.